A Study Combining ABT-888, Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
PCCTC-Prostate Cancer Clinical Trial Consortium
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01085422
First received: March 10, 2010
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

Assess whether the combination of ABT-888 with temozolomide (TMZ) has activity in subjects with metastatic castration resistant prostate cancer (CRPC) as reflected by the prostate-specific antigen (PSA) response.


Condition Intervention Phase
Prostate Cancer
Drug: ABT-888
Drug: temozolomide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Protein-specific antigen (PSA) test [ Time Frame: Day 0 through investigator-determined discontinuation (final visit) ] [ Designated as safety issue: Yes ]
    This is performed to assess if ABT-888 combined with temozolomide has activity in patients with prostate cancer as reflected by the prostate-specific antigen (PSA).


Secondary Outcome Measures:
  • Assessment of Efficacy [ Time Frame: Day 0 through investigator-determined discontinuation ] [ Designated as safety issue: Yes ]
    Evaluate the safety and tolerability of the combination therapy through safety assessments (i.e. electrocardiogram (ECG), clinical laboratory tests, vital signs, Adverse Event assessments, serious adverse events, physical exams, computed tomography (CT) scans)

  • Assessment of Safety [ Time Frame: Day 0 through survival follow-up ] [ Designated as safety issue: Yes ]
    Assess the objective response rate (ORR), PSA decline, time to progression (TTP), progression free survival (PFS), and overall survival (OS)


Enrollment: 35
Study Start Date: April 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A Drug: ABT-888
Subjects will be given ABT-888 on Days 1 -7 every 28 days orally and temozolomide on days 1-5 on days 1-5 every 28 days orally with ABT-888
Other Name: ABT-888, veliparib
Drug: temozolomide
Subjects will be given ABT-888 40 mg twice daily on Days 1 -7 every 28 days orally and temozolomide on days 1-5 every 28 days orally with ABT-888
Other Name: temozolomide

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has histologically or cytologically confirmed prostate cancer.
  • Metastatic prostate cancer with measurable and/or bony disease that has progressed despite androgen deprivation therapy and at least one and no more than two prior systemic non hormonal therapies (at least one must include docetaxel) for castration resistant metastatic disease.
  • At least 28 days must have elapsed since completion of prior anti-cancer therapy and must have recovered from all side effects to < Grade 1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. ECOG PS 3 is allowed if due to pain.
  • Subjects must have PSA progression defined as:

    • A 25% increase in PSA over a baseline value with an increase in the absolute value of PSA level by 2 ng/ml, that is confirmed by another PSA level at a minimum of 1 week interval.
  • Subjects must have a minimum PSA of > 2 ng/ml.
  • Testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy.
  • No investigational or commercial agents (other than LHRH analogue) or therapies including other hormonal agents such as antiandrogens or herbal medications may be administered with the intent to treat the subject's malignancy. Subjects on stable doses of steroids or megestrol acetate (for hot flashes or appetite) are allowed.
  • Four weeks must have elapsed since major surgery.
  • Prior radiotherapy is allowed as long as the bone marrow function is adequate and at least 4 weeks has elapsed since completion of radiation therapy. No prior radiopharmaceuticals are allowed.
  • Subjects must have normal organ and bone marrow function as defined below obtained within two weeks from treatment initiation:

    • Bone Marrow: absolute neutrophil count ≥ 1,500/mcL; platelets ≥ 100,000/mcL; hemoglobin ≥ 9.0 g/dL
    • Renal function: Serum creatinine ≤ 1.5 × upper limits of institution's normal (ULIN) range or creatinine clearance ≥ 50 mL/min/1.73 m2
    • Hepatic Function: Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤ 2.5 × ULIN. For subjects with liver metastases, AST and/or ALT < 5 × ULIN. Bilirubin ≤ 1.5 × ULIN (Subjects with Gilbert's Syndrome may have a bilirubin ≥ 1.5 × ULIN)
  • Subjects who refuse to provide blood samples for the correlative studies will be eligible.
  • ABT-888 and temozolomide are known to be teratogenic, therefore men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Subjects with treated and controlled epidural disease are permitted into the study.
  • Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.

Exclusion Criteria:

  • A subject with cord compression or a history of uncontrolled central nervous system (CNS) metastases or leptomeningeal disease.
  • Subject has had prior therapies with Dacarbazine (DTIC) or TMZ containing regimens.
  • The subject has received an investigational agent within 28 days prior to study drug administration.
  • Subject with a history of seizure disorder and currently receiving medications for seizure disorders (e.g., steroid or anticonvulsant drugs).
  • The subject has had another active malignancy within the past 1 year with the exception of definitely treated carcinomas in situ, superficial bladder cancer, and non-melanoma carcinoma of the skin. Questions regarding inclusion of individual subjects should be discussed with the Abbott Medical Monitor.
  • Clinically significant and uncontrolled major medical condition(s) including but not limited to:

    • active uncontrolled infection,
    • symptomatic congestive heart failure,
    • unstable angina pectoris or cardiac arrhythmia,
    • Psychiatric illness/social situation that would limit compliance with study requirements,
    • Or any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
  • Subject has previously been treated with a PARP inhibitor.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085422

Locations
United States, Maryland
Site Reference ID/Investigator# 25982
Baltimore, Maryland, United States, 21231-1000
United States, Michigan
Site Reference ID/Investigator# 26202
Ann Arbor, Michigan, United States, 48109-5946
United States, New York
Site Reference ID/Investigator# 27324
New York, New York, United States, 10065
United States, Oregon
Site Reference ID/Investigator# 27322
Portland, Oregon, United States, 97239
United States, Wisconsin
Site Reference ID/Investigator# 27323
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
PCCTC-Prostate Cancer Clinical Trial Consortium
Investigators
Study Director: Bhardwaj Desai, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01085422     History of Changes
Other Study ID Numbers: M11-070
Study First Received: March 10, 2010
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014